Use of recombinant gene delivery vectors for treating or preventing lysosomal storage disorders

Abstract

Gene delivery vectors, for example, recombinant FIV vectors, and methods of using such vectors are provided for use in treating or preventing retinal diseases of the eye and diseases of the brain associated with lysosomal storage disorders.

What is claimed is:  
     
       1. An FIV vector, comprising a 5′ FIV LTR, a tRNA binding site, a packaging signal, a promoter operably linked to a polynucleotide encoding a protein selected from the group consisting of β-glucuronidase, neuraminidase, sphingomyelinase, sulfatase, arylsulfatase β, α-neuraminidase, gangliosidase, tripeptidyl protease, CLN3, and palmitoyl protein thioesterase (PPT), an origin of second strand DNA synthesis and a 3′ FIV LTR, wherein the FIV vector is devoid of vif and ORF 2. 
     
     
       2. The FIV vector of  claim 1 , wherein the protein is β-glucuronidase. 
     
     
       3. An FIV vector particle comprising the FIV vector of  claim 1 . 
     
     
       4. A host cell transduced with the FIV vector particle of  claim 3 . 
     
     
       5. An FIV vector comprising a 5′ FIV LTR, a tRNA binding site, a packaging signal, a polynucleotide encoding β-glucuronidase operably linked to an FIV LTR promoter or a promoter element, an origin of second strand DNA synthesis and a 3′ FIV LTR, wherein the FIV vector is devoid of vif and ORF 2. 
     
     
       6. The FIV vector of  claim 5 , wherein the promoter element is a CMV, RSV or SV40 promoter. 
     
     
       7. An FIV vector particle comprising the FIV vector of  claim 5 . 
     
     
       8. A host cell transduced with the FIV vector particle of  claim 7 . 
     
     
       9. A method of treating a glucuronidase-related lysosomal storage disorder of the eye or brain comprising providing the FIV vector particle of  claim 7  to a vertebrate subject, wherein the FIV vector particle is administered to the subject in vivo, intravitreally, intraventricularly or via the striatum under conditions whereby the protein encoded by the polynucleotide is expressed in a cell of the vertebrate subject and secreted at a level sufficient to treat the lysosomal storage disorder. 
     
     
       10. The method of  claim 9 , wherein said lysosomal storage disorder is a disorder of the eye and is selected from the group consisting of macular degeneration, diabetic retinopathy, and inherited retinal degeneration. 
     
     
       11. The method of  claim 9 , wherein the lysosomal storage disorder is of the eye and the FIV vector particle is administered intravitreally. 
     
     
       12. The method of  claim 9 , wherein the lysosomal storage disorder is of the brain and the FIV vector particle is administered intraventricularly. 
     
     
       13. The method of  claim 9 , wherein the lysosomal storage disorder is of the brain and the FIV vector particle is administered via the striatum.